Glycogen

Glycogen is a polysaccharide that is the principal storage form of
glucose in animal cells. In humans and other vertebrates, most glycogen
is found in the skeletal muscles, but it is found in the highest concentration
in the liver (10% of the liver mass), giving it a distinctive, "starchy"
taste. In the muscles glycogen is found in a much lower concentration
(1% of the muscle mass). In addition, small amounts of glycogen are
found in the kidneys, and even smaller amounts in certain glial cells
in the brain and white blood cells.

Structure and biochemistry

Glycogen is a glucose polymer resembling the starch in plants (so it
is sometimes called "animal starch"). Glycogen is a highly
branched glucose polymer. It is formed of small chains of 8 to 12 glucose
molecules linked together with a (1?4) bonds. These small chains are
in turn linked together with a (1?6) bonds. A single molecule of glycogen
can be made of up to 120,000 molecules of glucose. It is stored in the
form of granules in the cytosol, or cell fluid.

These granules contain both glycogen and the necessary enzymes for
its conversion into glucose. It is generated from glucose by the enzyme
glycogen synthase. This process is called glycogenesis. The addition
of a glucose molecule to glycogen takes two high energy bonds: one from
ATP and one from UTP.

Its breakdown into glucose, called glycogenolysis, is mediated by the
enzyme glycogen phosphorylase. Its highly branched nature allows for
the quick retrieval of glucose molecules when needed.

Function and regulation of liver glycogen

As a carbohydrate meal is eaten and digested, blood glucose levels
rise, and the pancreas secretes insulin. Glucose from the portal vein
enters the liver cells (hepatocytes). Insulin acts on the hepatocytes
to stimulate the action of several enzymes, including glycogen synthase.
Glucose molecules are added to the chains of glycogen as long as both
insulin and glucose remain plentiful. In this postprandial or "fed"
state, the liver takes in more glucose from the blood than it releases.

After a meal has been digested and glucose levels begin to fall, insulin
secretion is reduced, and glycogen synthesis stops. About 4 hours after
a meal, glycogen begins to be broken down to be converted again to glucose.
Glycogen phosphorylase is the primary enzyme of glycogen breakdown.
For the next 8-12 hours, glucose derived from liver glycogen will be
the primary source of blood glucose to be used by the rest of the body
for fuel.

Glucagon is another hormone produced by the pancreas and in many respects
serves as a counter-signal to insulin. When the blood sugar begins to
fall below normal, glucagon is secreted in increasing amounts. It stimulates
glycogen breakdown into glucose even when insulin levels are abnormally
high.

Glycogen in muscle and other cells

Muscle cell glycogen appears to function as an immediate reserve source
of available glucose for muscle cells. Other cells that contain small
amounts use it locally as well. Muscle cells lack the ability to pass
glucose into the blood, so the glycogen they store internally is destined
for internal use and is not shared with other cells, unlike liver cells.

Disorders of glycogen metabolism

The most common disease in which glycogen metabolism becomes abnormal
is diabetes, in which, because of abnormal amounts of insulin, liver
glycogen can be abnormally accumulated or depleted. Restoration of normal
glucose metabolism usually normalizes glycogen metabolism as well.

In hypoglycemia caused by excessive insulin, liver glycogen levels
are high, but the high insulin level prevents the glycogenolysis necessary
to maintain normal blood sugar levels. Glucagon is a common treatment
for this type of hypoglycemia.

Various inborn errors of metabolism are caused by deficiencies of enzymes
necessary for glycogen synthesis or breakdown. These are collectively
referred to as glycogen storage diseases.